The applicant's group has recently cloned a new protein, Ebp1, which interacts with the cytoplasmic domain of the heregulin/neuregulin receptor, ErbB3. Ectopic expression of Ebp1 inhibits androgen dependent activation of androgen responsive reporter constructs. The purpose of this proposal is to understand the mechanism by which Ebp1 inhibits androgen receptor (AR) mediated transcription. The first specific aim will: (1) determine the ability of Ebp1 to modulate AR-mediated transcription from different wild type and natural androgen-responsive promoters and from endogenous genes; (2) determine the ability of Ebp1 to inhibit the activity of AR transcriptional coactivators; (3) determine if Ebp1 can inhibit ErbB2 induction of AR-mediated transactivation. In the second aim the applicant will: (1) confirm and extend the observation that AR and Ebp1 physically associate and (2) determine the regions of AR and Ebp1 needed for protein-protein binding. Deletion constructs generated will be used to determine if the inhibitory effects of Ebp1 on AR-mediated transcription and cell growth are related to the ability of this protein to bind AR.